The long range goal of this proposal is to develop near infrared (NIR) Raman spectroscopy as a quantitative method for in situ detection of atherosclerosis and its progression in human peripheral arteries. With this technique, information on chemical composition and molecular identity can be obtained rapidly, accurately, and remotely. Therefore, it has the potential to provide quantitative measurement of histochemical and histopathological markers for both the presence and extent of atherosclerotic alterations. The specific goals of our proposal are to: l) Investigate and validate the use of NIR Raman spectroscopy for diagnosis and prognosis of atherosclerosis in muscular and elastic arteries. We propose several approaches for characterizing fully the spectroscopic variability of the MR Raman signals with disease-associated alterations of artery, and establishing the detection sensitivity to different biochemical moieties and metabolites. We have planed specific experiments to compare Raman and chemical assays, correlate the spectral features observed at different stages of atherosclerosis with the morphological and molecular changes that take place, and use this information to establish diagnostic decision schemes. 2) Develop vibrational spectroscopy techniques for clinical applications. Detailed experiments are outlined to improve NIR Raman systems for clinical applications and build new spectroscopic systems, including a portable system for use in an operating room and Raman microprobes. 3) Confirm the validity of spectral models and diagnostic algorithms in preclinical studies. An in vivo study of the tissue alterations caused by atherosclerosis is proposed with the objective of determining the transferability of the technologies developed in vitro. The technique generated by this investigation will be broadly applicable to the characterization of disease in various human arteries and, more broadly, other tissue systems, and will establish the capability for real- time in vivo determination of human tissue histochemistry and pathobiology.